1. Field
Provided is a p15 protein variant; a polynucleotide encoding the p15 protein variant; a method for preparing the p15 protein variant; a pharmaceutical composition comprising the p15 protein variant; and a method for preventing and/or treating cancer comprising administering the p15 protein variant to a subject.
2. Description of the Related Art
p15INK4b (hereinafter abbreviated as “p15”) plays an important role in cell cycle regulation by decelerating the cell-cycle progression from the gap one phase (G1) to the DNA synthesis (S) phase (i.e., G1→S), a major check point (restriction point) responsible for the division of both normal and cancer cells. More specifically, p15 protein binds to cyclin-dependent kinase 4/6 (Cdk4/6) to arrest the cell proliferation (see, FIG. 1).
When p15 protein binds to Cdk4/6, the cell cycle progression from G1 phase to S phase (G1→S) is restricted, which, in turn, prohibits the subsequent events for cancer development including DNA synthesis in S phase and infinite cell division. Therefore, p15 protein can be effectively used as a tumor suppressor.
For cancer therapy using a p15 protein, it is required to provide a recombinant p15 protein having improved properties such as cell membrane permeability for delivering the protein into a cancer cell. However, expression of human p15 protein in E. coli cells presents problems The production of p15 protein is expressed in an insoluble form and exhibits low solubility and high flexibility (Yuan, C., et. al., 2000 Protein Science 1120-1128).
Thus, there is a need for a p15 protein variant with improved solubility that retains affinity to Cdk4/6, to provide for the effective application of p15 in cancer therapy.